The understanding of the interactions between the peptide components of the renin-angiotensin system (RAS) and both the enzymes responsible for their metabolism as well as the receptors for these hormones is the goal of this proposal. A practical translation of this understanding to yield specific inhibitors of renin, converting enzyme, and receptor interaction is a primary objective in hopes of providing a useful set of pharmacological tools for the study of the RAS in cardiovascular disease. Specifically, modifications to eliminate proteolytic degradation will be sought to provide orally active analogs. In addition, the concepts of transition state analogs and affinity labels will be used in the design of enzyme and receptor inhibitors. Finally, isolation and purification of the angiotensin receptor will be attempted from a variety of tissues in order to examine the basis for tissue-specific inhibitors as well as provide the foundation for reconstitution of a receptor-effector system in vitro.